HIPPOCAMPAL CA1 LACUNOSUM-MOLECULARE INTERNEURONS - COMPARISON OF EFFECTS OF ANOXIA ON EXCITATORY AND INHIBITORY POSTSYNAPTIC CURRENTS

1. The effects of anoxia on excitatory and inhibitory postsynaptic cur rents (EPSCs and IPSCs, respectively) evoked by electrical stimulation in the stratum radiatum were studied in morphologically and electroph ysiologicaly identified lacunosum-moleculare (LM) interneurons of the CA1 region of rat hippocampal slices. The blind whole cell patch-clamp technique was used, and anoxia was induced by superfusion of the slic e with an anoxic artificial cerebral spinal fluid saturated with 95% N -2-5% CO2 for 4-6 min. 2. In LM interneurons, anoxia generated current s similar to those in pyramidal cells, the most prominent being anoxic and postanoxic outward currents. The adenosine A(1) type receptor ant agonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM) did not sig nificantly affect anoxia-generated currents. 3. EPSCs and polysynaptic IPSCs (pIPSCs) evoked in LM interneurons by ''distant'' stimulation ( >1 mm) in the stratum radiatum were strongly depressed by anoxia and r ecovered upon reoxygenation. 4. Responses to pressure application of g lutamate, lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMP A), and N-methyl-D-aspartate (NMDA) were not significantly affected by anoxia, suggesting that the suppression of EPSCs is due to presynapti c mechanisms. 5. DPCPX(200 nM) prevented anoxia-induced suppression of EPSCs, suggesting that this suppression was mediated by presynaptic A (1) adenosine receptors. 6. Monosynaptic IPSCs evoked by ''close'' sti mulation (<0.5 mm) in the stratum radiatum, in the presence of glutama te-receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 mu M) and D-2-amino-5-phosphopentanoate (APV; 50 mu M), were reversib ly depressed but not blocked by anoxia. 7. Anoxia depressed monosynapt ic GABA(A) receptor-mediated IPSCs (monosynaptic IPSC(A)s) by inducing a positive shift in the reversal potential and a decrease in slope co nductance. Responses to pressure-applied isoguvacine, a GABA(A) recept or agonist, were reversibly depressed by anoxia, again because of a po sitive shift in reversal potential and decrease in conductance. Anoxic effects on slope conductances and reversal potential of isoguvacine r esponses and monosynaptic IPSCA coincided, suggesting that evoked tran smitter release from GABAergic terminals was not affected by anoxia. 8 . Anoxic depression of monosynaptic GABA(B) receptor-mediated IPSCs (m onosynaptic IPSC(B)s) was due to a decrease in the slope conductance o f monosynaptic IPSCB. In contrast to EPSCs, DPCPX (200 nM) failed to p revent anoxia-induced depression of mIPSC(A) and mIPSC(B). 9. Paired-p ulse depression of monosynaptic IPSCs, partially mediated by presynapt ic GABA(B) receptors, was not affected by anoxia. 10. These data provi de direct evidence for the hypothesis that inhibitory interneurons of CA1 stratum LM are functionally disconnected from excitatory inputs by anoxia. This disconnection underlies the preferential block by anoxia of IPSCs recorded in pyramidal cells, and it may occult the postsynap tic modifications in GABA(A) and GABA(B) responses. This disconnection involves adenosine-dependent inhibition of glutamate release from exc itatory terminals. GABA release and its modulation by presynaptic GABA (B) receptors, both known to be insensitive to adenosine, seems to be resistant to anoxia.